Insomnia’s Negative Sequelae On Mood: from Neuroscience to Intervention in the Aged

Project Information

INSOMNIA

Grant agreement ID: 671084

DOI

10.3030/671084

Project closed

EC signature date 13 October 2015

Start date 1 November 2015

End date 31 October 2021

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 867 360,98

EU contribution

€ 1 867 360,98

Coordinated by

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Netherlands

Periodic Reporting for period 4 - INSOMNIA (Insomnia’s Negative Sequelae On Mood: from Neuroscience to Intervention in the Aged)

Reporting period: 2020-05-01 to 2021-10-31

Summary of the context and overall objectives of the project

Major depression is among the most burdening health hazards. Its prevalence is 1-3%, an additional 8-16% have clinically significant symptoms, and prognosis is poor. Unfortunately, less than 20% of the cases are detected and treatment effectiveness is moderate. The Global Consortium for Depression Prevention stresses that our best chance to combat the global burden of depression is provide preventive intervention to identified people at risk. This project targets the strongest modifiable risk factor: insomnia. In an ground-breaking interdisciplinary way the project (1) identified the insomnia subtype that develops depression; (2) profiled mechanisms involved; and (3) optimized effectiveness of internet-supported home-applicable interventions to improve sleep and prevent depression. The findings facilitate immediate implementation of risk-based prevention strategies and policies.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We achieved all three objectives. We (1) enabled early identification of insomniacs at risk of depression. We (2) found clues to mechanisms underlying the increased risk by quantification of how insomniacs at risk differ from those that do not develop depression with respect to psychological traits, health history, life events, behavioural habits, environmental exposure, brain structure and brain function (PNAS 2016;113:2538; Lancet Psychiatry 2019;6:151; Brain 2019;142:1783; Sleep 2019;42:zsy268; Curr Biol 2019;29:2351; Transl Psychiatry 2020;10:425; Sleep 2020;zsaa031). We (3) demonstrated effectiveness of risk interventions (Psychother Psychosom 2021).
In more detail:
1. We established the profile of an individual’s psychological traits, health history, life events and brain structures involved in the risk of transitioning from insomnia to depression (Lancet Psychiatry 2019;6:151; Transl Psychiatry 2020;10:425; Sleep 2020;zsaa031). We identified brain functional correlates of maladaptive sleep (PNAS 2016;113:2538; Brain 2019;142:1783; Sleep 2019;42:zsy268; Curr Biol 2019;29:2351).
2. We developed the novel tool of network outcome analysis to demonstrate that the causal chain to the development of depression involves possibly modifiable behavioural and environmental factors that cause or maintain insomnia (Sleep 2020;43:zsz288).
3. We developed the novel tool of network intervention analysis to demonstrate that the causal chain to the development of depression could be acted upon by altering an individual’s modifiable behavioural and environmental factors that cause or maintain insomnia (Psychother Psychosom 2019;88:52). We demonstrated that acting on mentioned profile of an elderly individual’s modifiable behavioural and environmental factors interacting with this make-up to protect from transitioning from insomnia to depression.
4. We obtained the novel insight that insomnia mainly involves limbic circuits rather than sleep-regulating circuits of the brain (Nat Genet 2017;49:1584; Nat Genet 2019;51:394; Neurobiol Learn Mem 2019;160:144; Sleep 2020;zsaa031; Nat Genet 2022;in press). Acting on these limbic circuits could indeed be better targets for the development of novel preventive and therapeutic interventions (Physiol Rev 2021;101:995; PNAS 2016;113:2538; Brain 2019;142:1783; Sleep 2019;42:zsy268; Curr Biol 2019;29:2351).
5. For application in studies on novel interventions targeting specific factors discovered, we delivered diagnostic screening tools for profiling risk, ranging from a questionnaire for application in population-based screening (Lancet Psychiatry 2019;6:151; Sleep 2020;43:zsz288), to comprehensive genotyping (Nat Genet 2017;49:1584; Nat Genet 2019;51:394; Nat Genet 2022;in press) and phenotyping of brain structure (Transl Psychiatry 2020;10:425; Sleep 2020;zsaa031) and brain function (PNAS 2016;113:2538; Brain 2019;142:1783; Sleep 2019;42:zsy268; Curr Biol 2019;29:2351).
6. In a randomized controlled trial, we compared internet-based cognitive behavioural therapy for insomnia (CBT-I), chronotherapy (CT), and their combination to reveal the optimally effective and most cost-effective intervention to date to prevent depression in insomniacs at risk of developing it (Psychother Psychosom 2021).
7. We communicated this finding as best practice recommendation for implementation of the evidence-based most effective presently available intervention to prevent conversion of insomnia to depression (Psychother Psychosom 2021).

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

As to novel methodologies, we developed an innovative method to study self-conscious emotions which interfere most with mental health, but are rarely studied due to a scarcity of quantitative tools for their induction and assessment. The paradigm met with great enthusiasm of leading emotion researchers, one of which commented "I see this karaoke paradigm as being the invention of the century in experimental stress research". The paradigm revealed mechanisms that impede overnight amelioration of distress and promote development of depression, posttraumatic stress disorders and anxiety disorders (PNAS 2016;113:2538; Brain 2019;142:1783; Sleep 2019;42:zsy268; Curr Biol 2019;29:2351; Physiol Rev 2021;101:995).

We integrated cognitive behavioural therapy for insomnia (CBT-I) with chronotherapy (CT), to provide the most cost-effective intervention to date to prevent depression in insomniacs at risk of developing it (Psychother Psychosom 2021). We attained a genetic understanding of the vulnerability to insomnia and the consequential risk of other mental health issues (Nat Genet 2017;49:1584; Nat Genet 2019;51:394; Nat Genet 2022;in press). We connected the separated research fields on emotion regulation and sleep (Physiol Rev 2021;101:995). We discovered that sleep can be maladaptive (Physiol Rev 2021;101:995). We connected the separated research field on circadian rhythms with current clinical approaches (Psychother Psychosom 2021).

As to knowledge and technology transfer, our “karaoke” paradigm was adopted by several other labs. Our insomnia intervention is now implemented to treat insomnia to enhance recovery from posttraumatic stress and anxiety disorders (Psychother Psychosom 2021). Our polygenic risk scores (PRS) for insomnia can now be calculated for studies into genetic vulnerability (Nat Genet 2017;49:1584; Nat Genet 2019;51:394; Nat Genet 2022;in press). We outlined how to quantify emotionally maladaptive sleep (Curr Biol 2019;29:2351). We showed how molecular neuroscience level can address mechanisms of maladaptive sleep-facilitated synaptic plasticity in the limbic circuits of the brain (Physiol Rev 2021;101:995).

Higlights of transfer of knowledge and technology to scientists, clinicians and the general public. Just a few highlights were front-page news on Britain's major newspaper The Times (Whipple 26/04/19), an item in USA's most prestigious documentary series NOVA, and as one of only three insomnia researchers in 35 years, having had the honour of being invited to give the presidential address keynote at the opening ceremony of the largest, most important scientific meeting on sleep (SLEEP 2021).

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